Mix-and-match between transposable elements and zinc finger proteins fuels genic and regulatory innovation

Transposable elements (TEs) are abundant and dynamic components of eukaryotic genomes, subject to regulation by equally adaptive regulatory systems. A coevolution of TEs and zinc finger genes can be documented throughout metazoan evolution. In humans, TEs account for half of the genome, and nearly all TE subfamilies are preferentially bound by at least one of the approximately 400 KRAB zinc finger proteins (ZFPs). The majority of human KRAB-ZFPs appear to tame the cis-regulatory activities of TEs, thereby facilitating their integration within gene regulatory networks. In turn, throughout vertebrate evolution, TE protein domains have fused repeatedly with ZFPs to give rise to new classes of regulatory proteins. Thus, the TE-ZFP interplay has been a powerful catalyst of biological innovation.